Neuropeptides involved in the pathophysiology of schizophrenia and major depression.

The present review summarizes the findings on the role of neuropeptides in the pathophysiology of schizophrenia and major depression. Several neuropeptides as vasopressin and endorphins in particular, beta-endorphin and gamma-type endorphins, cholecystokinin (CCK), neurotensin, somatostatin and Neuropeptide Y have been implicated in schizophrenia. During the last decade, however, few attempts to explore the significance of most of these and other neuropeptides in the pathophysiology of the disease or their therapeutic potential are found in the literature. An exception is neurotensin, which exerts neuroleptic-like effects in animal studies, while CSF, brain and blood studies are inconclusive. Things are different in major depression. Here much attention is paid to the endocrine abnormalities found in this disorder in particular the increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. Neuropeptides as corticotropin-releasing hormone (CRH), vasopressin and corticosteroids are implicated in the symptomatology of this disorder. As a consequence much work is going on investigating the influence of CRH and corticosteroid antagonists or inhibitors of the synthesis of corticosteroids as potential therapeutic agents. This review emphasizes the role of vasopressin in the increased activity of the HPA axis in major depression and suggests exploration of the influence of the now available non-peptidergic vasopressin orally active V1 antagonists.